Pharmacotherapy for Pregnant Women with Opioid Use Disorder

1 Introduction

This project focuses on Analysis 2 of the Study Protocol, which aims to characterize pregnant individuals with OUD and examine hazards of maternal death and overdose. A poster was presented at Academy Health annual research meeting focusing on analysis on those with OUD and at least one day of MOUD prescription. (Section 7)

2 Study Flow Chart

• Methadone exclusion: n=0 (TennCare OTP coverage began June 2020). Follow-up >1 year exclusion: n=0 (days to event already capped at 365 days).

2.1 Methods

Data Source

• TennCare data
• TN all payer hospitalization database
• Birth and death certificates
• US Census data

Inclusion Criteria

• Women 15-44 years old
• Delivery of an infant >=20 weeks between 2007-2020
• Continuous enrollment in TennCare from 90 pre-delivery through 41 days post partum
• No sickle cell disease or active malignancy
• With and without MOUD receipt initially, but only included those with MOUD for main analysis
• Up to 5-days gap of continuous enrollment

• Exposure: Days of MOUD supply between -90 days prior to delivery and +41 days post-delivery (maximum number of days = 132)
• Covariates also collected during exposure period
• Outcomes: first event of either overdose or death from 42 days post-delivery

Statistical analysis

Descriptive statistics were computed using frequencies (proportions) and medians (IQRs) as appropriate for the overall sample and also stratified by timing of MOUD receipt. Timing of MOUD receipt variable was categorized relative to timing of delivery and has two levels: receipt during one period only either pre- or post-delivery or receipt during both pre- and post-delivery periods. Due to the low number of outcomes, several variables were collapsed into one. These variables are listed below.

• Route of delivery: Cesarean or Vaginal (Vaginal + Forcep + Vacuum)
• Pain conditions: Back pain + dental pain + fibromyalgia + indicator for NSAIDs
• Alcohol use disorder + other substance use
• Benzodiazepine + Anticonvulsant use
• Anxiety + Depression

After calculating the number of days of MOUD receipt, various histograms were plotted to examine differences by method. Then, multivariable Cox Proportional hazards model were used to determine the associations between total days of MOUD receipt as the main exposure and death or overdose as the outcome. For individuals with multiple outcomes, the earliest outcome was used. Outcomes that occurred during the follow-up period were counted if they were captured in the TN all payer database if an individual lost eligibility for TennCare. Average dose per day of MOUD receipt (qty*dose)/(days supply) was also calculated and described in the table. Average days supply and dose from the pre-delivery period that exceeded 90 days was carried over and added to the post-delivery period.

The Cox model was first modeled using linear continuous terms, due to the limited degrees of freedom. However, year of delivery was determined to be non-linear and was modeled using a restricted cubic spline with 3 knots. These models included the following covariates: year of delivery, total day MOUD receipt, age at delivery, gestation weeks, route of delivery, combined pain conditions, alcohol/other substance use, benzodiazepine/anticonvulsant use, anxiety/depression, maternal morbidity (CDC defined). Additional covariates were included initially but were removed due to the small number of outcomes. These include race/ethnicity combined, number of previous pregnancies, schizophrenia/personality disorder, CDC social vulnerability index, and timing of MOUD receipt (one or two periods relative to delivery). Robust standard errors clustered at the individual level were computed.

Additonal notes: few outcomes (<5) prior to 2015

3 Only including data of women with MOUD receipt

3.1 Descriptive Statistics

• There are 9048 pregnancies in 7559 unique individuals

  	N	Overall
  		(N=9419)
  Year of delivery	9419 (100.00)
  Median (interquartile range)		2016 (2014—2018)
  Range		2007—2020
  Age at delivery	9419 (100.00)
  Median (interquartile range)		27 (24—31)
  Range		17—44
  Number of Gestation weeks	9419 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	9385 (99.64)
  American Indian or Alaska Native		24/9385 (0.26)
  Asian or Pacific Islander		12/9385 (0.13)
  Black of African American		252/9385 (2.69)
  Other or Unknown		62/9385 (0.66)
  White		9035/9385 (96.27)
  Hispanic : Not Hispanic	9378 (99.56)	9298/9378 (99.15)
  Race/Ethnicity combined	9385 (99.64)
  Hispanic		80/9385 (0.85)
  Non-Hispanic Asian		11/9385 (0.12)
  Non-Hispanic Black		250/9385 (2.66)
  Non-Hispanic Other		62/9385 (0.66)
  Non-Hispanic White		8982/9385 (95.71)
  Route of delivery : Vaginal	9385 (99.64)	6122/9385 (65.23)
  Number of previous pregnancies	9219 (97.88)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	9419 (100.00)
  Death		39/9419 (0.41)
  Overdose		109/9419 (1.16)
  Loss of enrollment		1059/9419 (11.24)
  Censored		8212/9419 (87.19)
  Final outcome (w/o all payer data)	9419 (100.00)
  Death		15/9419 (0.16)
  Overdose		103/9419 (1.09)
  Loss of enrollment		1089/9419 (11.56)
  Censored		8212/9419 (87.19)
  Total days supplied MOUD	9419 (100.00)
  Median (interquartile range)		93 (50—120)
  Range		1—132
  Total days supplied MOUD before delivery	9419 (100.00)
  Median (interquartile range)		73 (30—90)
  Range		0—90
  Total days supplied MOUD after delivery	9419 (100.00)
  Median (interquartile range)		30 (7—42)
  Range		0—42
  Total days supplied MOUD (method 2)	9419 (100.00)
  Median (interquartile range)		97 (50—124)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	9419 (100.00)
  Median (interquartile range)		73 (30—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	9419 (100.00)
  Median (interquartile range)		30 (12—42)
  Range		0—42
  Total days supplied MOUD (method 3)	9419 (100.00)
  Median (interquartile range)		88 (43—111)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	9419 (100.00)
  Median (interquartile range)		62 (28—77)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	9419 (100.00)
  Median (interquartile range)		30 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	9327 (99.02)
  Median (interquartile range)		14.00 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	9327 (99.02)
  Median (interquartile range)		9.85 (4.00—16.00)
  Range		0.00—53.57
  Avg dose exposure (mg)	9327 (99.02)
  Median (interquartile range)		14.12 (9.42—16.00)
  Range		0.00—53.57
  Total days buprenorphine before delivery (method 3)	9187 (97.54)
  Median (interquartile range)		62.00 (29.00—78.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	9187 (97.54)
  Median (interquartile range)		30.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	9187 (97.54)
  Median (interquartile range)		89.00 (45.00—112.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	9186 (97.53)
  Median (interquartile range)		13.86 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	9186 (97.53)
  Median (interquartile range)		9.86 (4.00—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	9186 (97.53)
  Median (interquartile range)		14.00 (9.15—16.00)
  Range		0.00—42.67
  Type of MOUD	9419 (100.00)
  Both		103/9419 (1.09)
  Buprenorphine only		9084/9419 (96.44)
  Naltrexone only		232/9419 (2.46)
  Combined pain : Yes	9419 (100.00)	7216/9419 (76.61)
  Schizophrenia or personality disorder : Yes	9419 (100.00)	679/9419 (7.21)
  Alcohol or other substance use : Yes	9419 (100.00)	4009/9419 (42.56)
  Benzodiazepine or anticonvulsant use : Yes	9419 (100.00)	1306/9419 (13.87)
  Maternal morbidity : Yes	9419 (100.00)	638/9419 (6.77)
  Anxiety and depression combined : Yes	9419 (100.00)	4098/9419 (43.51)
  Back pain : Yes	9419 (100.00)	3205/9419 (34.03)
  Depression : Yes	9419 (100.00)	3498/9419 (37.14)
  Bipolar disorder : Yes	9419 (100.00)	918/9419 (9.75)
  Other substance use : Yes	9419 (100.00)	3826/9419 (40.62)
  Tobacco use : Yes	9419 (100.00)	6286/9419 (66.74)
  Med NSAIDS : Yes	9419 (100.00)	5742/9419 (60.96)
  Schizophrenia psychotic disorders : Yes	9419 (100.00)	544/9419 (5.78)
  Anxiety : Yes	9419 (100.00)	1774/9419 (18.83)
  Med benzodiazepine use : Yes	9419 (100.00)	894/9419 (9.49)
  Maternal morbidity : Yes	9419 (100.00)	638/9419 (6.77)
  Dental pain : Yes	9419 (100.00)	352/9419 (3.74)
  Alcohol use disorder : Yes	9419 (100.00)	564/9419 (5.99)
  Med anticonvulsant use : Yes	9419 (100.00)	497/9419 (5.28)
  Med muscle relaxant use : Yes	9419 (100.00)	455/9419 (4.83)
  Personality disorder : Yes	9419 (100.00)	248/9419 (2.63)
  Fibromyalgia : Yes	9419 (100.00)	458/9419 (4.86)
  CDC SVI overall percentile ranking of all 4 themes	8781 (93.23)
  Median (interquartile range)		0.58 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.
  
  

3.2 By cases

	N	No outcome	Had outcome	Test Statistic
		(N=9271)	(N=148)
Year of delivery	9419 (100.00)			F1,9417=39.74, P<0.00013
Median (interquartile range)		2016 (2014—2018)	2018 (2016—2019)
Range		2007—2020	2007—2020
Age at delivery	9419 (100.00)			F1,9417=0.58, P=0.44533
Median (interquartile range)		27 (24—31)	27 (25—31)
Range		17—44	19—41
Number of Gestation weeks	9419 (100.00)			F1,9417=7.00, P=0.00823
Median (interquartile range)		39 (37—39)	38 (37—39)
Range		21—42	25—42
Race	9385 (99.64)			Χ2 4=28.01, P<0.00012
American Indian or Alaska Native		23/9237 (0.25)	1/148 (0.68)
Asian or Pacific Islander		12/9237 (0.13)	0/148 (0.00)
Black of African American		247/9237 (2.67)	5/148 (3.38)
Other or Unknown		56/9237 (0.61)	6/148 (4.05)
White		8899/9237 (96.34)	136/148 (91.89)
Hispanic : Not Hispanic	9378 (99.56)	9152/9230 (99.15)	146/148 (98.65)	Χ2 1=0.44, P=0.50642
Race/Ethnicity combined	9385 (99.64)			Χ2 4=27.43, P<0.00012
Hispanic		78/9237 (0.84)	2/148 (1.35)
Non-Hispanic Asian		11/9237 (0.12)	0/148 (0.00)
Non-Hispanic Black		245/9237 (2.65)	5/148 (3.38)
Non-Hispanic Other		56/9237 (0.61)	6/148 (4.05)
Non-Hispanic White		8847/9237 (95.78)	135/148 (91.22)
Route of delivery : Vaginal	9385 (99.64)	6026/9237 (65.24)	96/148 (64.86)	Χ2 1=0.01, P=0.92472
Number of previous pregnancies	9219 (97.88)			F1,9217=1.25, P=0.26283
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—12
Final outcome	9419 (100.00)			Χ2 3=9419.00, P<0.00012
Death		0/9271 (0.00)	39/148 (26.35)
Overdose		0/9271 (0.00)	109/148 (73.65)
Loss of enrollment		1059/9271 (11.42)	0/148 (0.00)
Censored		8212/9271 (88.58)	0/148 (0.00)
Final outcome (w/o all payer data)	9419 (100.00)			Χ2 3=7532.70, P<0.00012
Death		0/9271 (0.00)	15/148 (10.14)
Overdose		0/9271 (0.00)	103/148 (69.59)
Loss of enrollment		1059/9271 (11.42)	30/148 (20.27)
Censored		8212/9271 (88.58)	0/148 (0.00)
Total days supplied MOUD (method 3)	9419 (100.00)			F1,9417=9.33, P=0.00233
Median (interquartile range)		88 (43—111)	72 (30—106)
Range		1—132	2—131
Total days supplied MOUD before delivery (method 3)	9419 (100.00)			F1,9417=5.28, P=0.02163
Median (interquartile range)		62 (29—77)	53 (17—76)
Range		0—90	0—89
Total days supplied MOUD after delivery (method 3)	9419 (100.00)			F1,9417=10.26, P=0.00143
Median (interquartile range)		30 (12—40)	22 (6—36)
Range		0—42	0—42
Avg dose pre-delivery (mg)	9327 (99.02)			F1,9325=1.10, P=0.29423
Median (interquartile range)		14.00 (8.00—16.00)	12.66 (6.38—16.00)
Range		0.00—50.00	0.00—50.00
Avg dose post-delivery (mg)	9327 (99.02)			F1,9325=0.38, P=0.53903
Median (interquartile range)		9.86 (4.00—16.00)	9.13 (0.00—16.00)
Range		0.00—53.57	0.00—31.00
Avg dose exposure (mg)	9327 (99.02)			F1,9325=0.06, P=0.80253
Median (interquartile range)		14.12 (9.45—16.00)	13.83 (8.40—16.00)
Range		0.00—53.57	1.00—50.00
Total days buprenorphine before delivery (method 3)	9187 (97.54)			F1,9185=6.90, P=0.00873
Median (interquartile range)		62.00 (30.00—78.00)	49.00 (17.67—76.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	9187 (97.54)			F1,9185=13.82, P=0.00023
Median (interquartile range)		30.00 (12.00—40.00)	22.00 (5.00—36.00)
Range		0.00—42.00	0.00—42.00
Total days supplied buprenorphine	9187 (97.54)			F1,9185=12.02, P=0.00053
Median (interquartile range)		89.00 (45.00—112.00)	71.00 (28.00—105.67)
Range		1.00—132.00	2.00—131.00
Avg dose BUP pre-delivery (mg)	9186 (97.53)			F1,9184=2.08, P=0.14933
Median (interquartile range)		13.87 (8.00—16.00)	12.44 (6.14—16.00)
Range		0.00—40.00	0.00—24.24
Avg dose BUP post-delivery (mg)	9186 (97.53)			F1,9184=0.13, P=0.71753
Median (interquartile range)		9.87 (4.00—16.00)	9.18 (0.00—16.00)
Range		0.00—42.67	0.00—31.00
Avg dose BUP exposure (mg)	9186 (97.53)			F1,9184=0.00, P=0.97753
Median (interquartile range)		14.00 (9.18—16.00)	13.36 (8.38—16.00)
Range		0.00—42.67	1.00—31.00
Combined pain : Yes	9419 (100.00)	7110/9271 (76.69)	106/148 (71.62)	Χ2 1=2.09, P=0.14842
Schizophrenia or personality disorder : Yes	9419 (100.00)	658/9271 (7.10)	21/148 (14.19)	Χ2 1=10.95, P=0.00092
Alcohol or other substance use : Yes	9419 (100.00)	3937/9271 (42.47)	72/148 (48.65)	Χ2 1=2.28, P=0.13122
Benzodiazepine or anticonvulsant use : Yes	9419 (100.00)	1278/9271 (13.78)	28/148 (18.92)	Χ2 1=3.21, P=0.07302
Maternal morbidity : Yes	9419 (100.00)	628/9271 (6.77)	10/148 (6.76)	Χ2 1=0.00, P=0.99352
Anxiety and depression combined : Yes	9419 (100.00)	4004/9271 (43.19)	94/148 (63.51)	Χ2 1=24.48, P<0.00012
Back pain : Yes	9419 (100.00)	3170/9271 (34.19)	35/148 (23.65)	Χ2 1=7.21, P=0.00722
Depression : Yes	9419 (100.00)	3411/9271 (36.79)	87/148 (58.78)	Χ2 1=30.18, P<0.00012
Bipolar disorder : Yes	9419 (100.00)	887/9271 (9.57)	31/148 (20.95)	Χ2 1=21.44, P<0.00012
Other substance use : Yes	9419 (100.00)	3756/9271 (40.51)	70/148 (47.30)	Χ2 1=2.78, P=0.09552
Tobacco use : Yes	9419 (100.00)	6179/9271 (66.65)	107/148 (72.30)	Χ2 1=2.09, P=0.14792
Med NSAIDS : Yes	9419 (100.00)	5655/9271 (61.00)	87/148 (58.78)	Χ2 1=0.30, P=0.58402
Schizophrenia psychotic disorders : Yes	9419 (100.00)	525/9271 (5.66)	19/148 (12.84)	Χ2 1=13.78, P=0.00022
Anxiety : Yes	9419 (100.00)	1727/9271 (18.63)	47/148 (31.76)	Χ2 1=16.43, P=0.00012
Med benzodiazepine use : Yes	9419 (100.00)	879/9271 (9.48)	15/148 (10.14)	Χ2 1=0.07, P=0.78772
Maternal morbidity : Yes	9419 (100.00)	628/9271 (6.77)	10/148 (6.76)	Χ2 1=0.00, P=0.99352
Dental pain : Yes	9419 (100.00)	345/9271 (3.72)	7/148 (4.73)	Χ2 1=0.41, P=0.52112
Alcohol use disorder : Yes	9419 (100.00)	540/9271 (5.82)	24/148 (16.22)	Χ2 1=27.94, P<0.00012
Med anticonvulsant use : Yes	9419 (100.00)	481/9271 (5.19)	16/148 (10.81)	Χ2 1=9.21, P=0.00242
Med muscle relaxant use : Yes	9419 (100.00)	446/9271 (4.81)	9/148 (6.08)	Χ2 1=0.51, P=0.47452
Personality disorder : Yes	9419 (100.00)	241/9271 (2.60)	7/148 (4.73)	Χ2 1=2.58, P=0.10832
Fibromyalgia : Yes	9419 (100.00)	451/9271 (4.86)	7/148 (4.73)	Χ2 1=0.01, P=0.93972
CDC SVI overall percentile ranking of all 4 themes	8781 (93.23)			F1,8779=0.67, P=0.41233
Median (interquartile range)		0.58 (0.37—0.78)	0.54 (0.33—0.81)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.3 MOUD information

	N	All
		(N=9419)
MOUD pre-delivery (method 1)	9419 (100.00)
No MOUD		868/9419 (9.22)
MOUD		8551/9419 (90.78)
MOUD pre-delivery (method 2)	9419 (100.00)
No MOUD		868/9419 (9.22)
MOUD		8551/9419 (90.78)
MOUD pre-delivery (method 3)	9419 (100.00)
No MOUD		875/9419 (9.29)
MOUD		8544/9419 (90.71)
MOUD post-delivery (method 1)	9419 (100.00)
No MOUD		1971/9419 (20.93)
MOUD		7448/9419 (79.07)
MOUD post-delivery (method 2)	9419 (100.00)
No MOUD		1740/9419 (18.47)
MOUD		7679/9419 (81.53)
MOUD post-delivery (method 3)	9419 (100.00)
No MOUD		1236/9419 (13.12)
MOUD		8183/9419 (86.88)
MOUD pre and post (method 1)	9419 (100.00)
No MOUD		0/9419 (0.00)
Both pre and post		6580/9419 (69.86)
Either pre or post		2839/9419 (30.14)
MOUD pre and post (method 2)	9419 (100.00)
No MOUD		0/9419 (0.00)
Both pre and post		6811/9419 (72.31)
Either pre or post		2608/9419 (27.69)
MOUD pre and post (method 3)	9419 (100.00)
No MOUD		0/9419 (0.00)
Both pre and post		7308/9419 (77.59)
Either pre or post		2111/9419 (22.41)

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.4 Characteristics based on MOUD timing (method 3)

3.4.1 Two categories

	N	Both pre and post	Either pre or post	Test Statistic
		(N=7308)	(N=2111)
Year of delivery	9419 (100.00)			F1,9417=6.34, P=0.01183
Median (interquartile range)		2016 (2014—2018)	2016 (2014—2018)
Range		2007—2020	2007—2020
Year of delivery as categorical	9419 (100.00)			Χ2 13=57.13, P<0.00012
2007		37/7308 (0.51)	17/2111 (0.81)
2008		80/7308 (1.09)	45/2111 (2.13)
2009		135/7308 (1.85)	46/2111 (2.18)
2010		217/7308 (2.97)	68/2111 (3.22)
2011		265/7308 (3.63)	75/2111 (3.55)
2012		364/7308 (4.98)	77/2111 (3.65)
2013		577/7308 (7.90)	132/2111 (6.25)
2014		787/7308 (10.77)	177/2111 (8.38)
2015		962/7308 (13.16)	242/2111 (11.46)
2016		874/7308 (11.96)	261/2111 (12.36)
2017		729/7308 (9.98)	257/2111 (12.17)
2018		721/7308 (9.87)	243/2111 (11.51)
2019		737/7308 (10.08)	241/2111 (11.42)
2020		823/7308 (11.26)	230/2111 (10.90)
Age at delivery	9419 (100.00)			F1,9417=5.60, P=0.01803
Median (interquartile range)		27 (24—31)	27 (24—30)
Range		17—44	17—44
Number of Gestation weeks	9419 (100.00)			F1,9417=11.23, P=0.00083
Median (interquartile range)		39 (37—39)	39 (37—39)
Range		21—42	23—42
Race	9385 (99.64)			Χ2 4=8.20, P=0.08462
American Indian or Alaska Native		17/7282 (0.23)	7/2103 (0.33)
Asian or Pacific Islander		10/7282 (0.14)	2/2103 (0.10)
Black of African American		180/7282 (2.47)	72/2103 (3.42)
Other or Unknown		44/7282 (0.60)	18/2103 (0.86)
White		7031/7282 (96.55)	2004/2103 (95.29)
Hispanic : Not Hispanic	9378 (99.56)	7215/7279 (99.12)	2083/2099 (99.24)	Χ2 1=0.26, P=0.60772
Race/Ethnicity combined	9385 (99.64)			Χ2 4=11.22, P=0.02422
Hispanic		64/7282 (0.88)	16/2103 (0.76)
Non-Hispanic Asian		9/7282 (0.12)	2/2103 (0.10)
Non-Hispanic Black		180/7282 (2.47)	70/2103 (3.33)
Non-Hispanic Other		40/7282 (0.55)	22/2103 (1.05)
Non-Hispanic White		6989/7282 (95.98)	1993/2103 (94.77)
Route of delivery : Vaginal	9385 (99.64)	4703/7282 (64.58)	1419/2103 (67.48)	Χ2 1=6.01, P=0.01422
Number of previous pregnancies	9219 (97.88)			F1,9217=0.02, P=0.88683
Median (interquartile range)		2 (1—3)	2 (1—3)
Range		0—23	0—23
Final outcome	9419 (100.00)			Χ2 3=25.75, P<0.00012
Death		30/7308 (0.41)	9/2111 (0.43)
Overdose		72/7308 (0.99)	37/2111 (1.75)
Loss of enrollment		770/7308 (10.54)	289/2111 (13.69)
Censored		6436/7308 (88.07)	1776/2111 (84.13)
Final outcome 3 levels	9419 (100.00)			Χ2 2=8.45, P=0.01462
Death		30/7308 (0.41)	9/2111 (0.43)
Overdose		72/7308 (0.99)	37/2111 (1.75)
Censored		7206/7308 (98.60)	2065/2111 (97.82)
Total days supplied MOUD	9419 (100.00)			F1,9417=7245.94, P<0.00013
Median (interquartile range)		108 (85—122)	29 (14—42)
Range		2—132	1—90
Total days supplied MOUD before delivery	9419 (100.00)			F1,9417=5459.01, P<0.00013
Median (interquartile range)		84 (60—90)	10 (0—32)
Range		1—90	0—90
Total days supplied MOUD after delivery	9419 (100.00)			F1,9417=2399.46, P<0.00013
Median (interquartile range)		30 (21—42)	0 (0—21)
Range		0—42	0—42
Total days supplied MOUD (method 2)	9419 (100.00)			F1,9417=7098.36, P<0.00013
Median (interquartile range)		112 (85—129)	29 (14—42)
Range		2—132	1—132
Total days supplied MOUD before delivery (method 2)	9419 (100.00)			F1,9417=5459.01, P<0.00013
Median (interquartile range)		84 (60—90)	10 (0—32)
Range		1—90	0—90
Total days supplied MOUD after delivery (method 2)	9419 (100.00)			F1,9417=2914.89, P<0.00013
Median (interquartile range)		35 (24—42)	0 (0—22)
Range		0—42	0—42
Total days supplied MOUD (method 3)	9419 (100.00)			F1,9417=7301.94, P<0.00013
Median (interquartile range)		100 (76—116)	21 (10—33)
Range		2—132	1—89
Total days supplied MOUD before delivery (method 3)	9419 (100.00)			F1,9417=4546.96, P<0.00013
Median (interquartile range)		69 (49—80)	9 (0—30)
Range		1—90	0—89
Total days supplied MOUD after delivery (method 3)	9419 (100.00)			F1,9417=5868.95, P<0.00013
Median (interquartile range)		35 (23—41)	0 (0—11)
Range		1—42	0—41
Avg dose pre-delivery (mg)	9327 (99.02)			F1,9325=1018.74, P<0.00013
Median (interquartile range)		14.90 (9.76—16.00)	7.33 (0.00—16.00)
Range		0.25—50.00	0.00—50.00
Avg dose post-delivery (mg)	9327 (99.02)			F1,9325=1081.32, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—12.29)
Range		0.00—50.00	0.00—53.57
Avg dose exposure (mg)	9327 (99.02)			F1,9325=7.49, P=0.00623
Median (interquartile range)		14.02 (9.83—16.00)	15.00 (8.00—16.00)
Range		0.25—50.00	0.00—53.57
Total days buprenorphine before delivery (method 3)	9187 (97.54)			F1,9185=4050.62, P<0.00013
Median (interquartile range)		69.00 (49.00—80.00)	12.00 (0.00—32.00)
Range		0.00—90.00	0.00—89.00
Total days buprenorphine after delivery (method 3)	9187 (97.54)			F1,9185=5433.57, P<0.00013
Median (interquartile range)		35.00 (23.00—41.00)	0.00 (0.00—9.00)
Range		0.00—42.00	0.00—41.00
Total days supplied buprenorphine	9187 (97.54)			F1,9185=6525.03, P<0.00013
Median (interquartile range)		100.00 (76.00—116.00)	21.00 (10.00—34.00)
Range		2.00—132.00	1.00—89.00
Avg dose BUP pre-delivery (mg)	9186 (97.53)			F1,9184=1053.07, P<0.00013
Median (interquartile range)		14.77 (9.54—16.00)	7.00 (0.00—15.63)
Range		0.00—40.00	0.00—32.00
Avg dose BUP post-delivery (mg)	9186 (97.53)			F1,9184=1143.86, P<0.00013
Median (interquartile range)		12.00 (8.00—16.00)	0.00 (0.00—12.00)
Range		0.00—33.24	0.00—42.67
Avg dose BUP exposure (mg)	9186 (97.53)			F1,9184=1.28, P=0.25873
Median (interquartile range)		13.95 (9.71—16.00)	14.48 (8.00—16.00)
Range		0.25—34.47	0.00—42.67
Combined pain : Yes	9419 (100.00)	5617/7308 (76.86)	1599/2111 (75.75)	Χ2 1=1.14, P=0.28652
Schizophrenia or personality disorder : Yes	9419 (100.00)	496/7308 (6.79)	183/2111 (8.67)	Χ2 1=8.67, P=0.00322
Alcohol or other substance use : Yes	9419 (100.00)	3077/7308 (42.10)	932/2111 (44.15)	Χ2 1=2.80, P=0.09412
Benzodiazepine or anticonvulsant use : Yes	9419 (100.00)	1034/7308 (14.15)	272/2111 (12.88)	Χ2 1=2.19, P=0.13882
Maternal morbidity : Yes	9419 (100.00)	490/7308 (6.70)	148/2111 (7.01)	Χ2 1=0.24, P=0.62222
Anxiety and depression combined : Yes	9419 (100.00)	3174/7308 (43.43)	924/2111 (43.77)	Χ2 1=0.08, P=0.78212
Back pain : Yes	9419 (100.00)	2516/7308 (34.43)	689/2111 (32.64)	Χ2 1=2.34, P=0.12642
Depression : Yes	9419 (100.00)	2700/7308 (36.95)	798/2111 (37.80)	Χ2 1=0.51, P=0.47332
Bipolar disorder : Yes	9419 (100.00)	713/7308 (9.76)	205/2111 (9.71)	Χ2 1=0.00, P=0.95062
Other substance use : Yes	9419 (100.00)	2924/7308 (40.01)	902/2111 (42.73)	Χ2 1=5.02, P=0.02512
Tobacco use : Yes	9419 (100.00)	4874/7308 (66.69)	1412/2111 (66.89)	Χ2 1=0.03, P=0.86792
Med NSAIDS : Yes	9419 (100.00)	4469/7308 (61.15)	1273/2111 (60.30)	Χ2 1=0.50, P=0.48122
Schizophrenia psychotic disorders : Yes	9419 (100.00)	401/7308 (5.49)	143/2111 (6.77)	Χ2 1=4.98, P=0.02562
Anxiety : Yes	9419 (100.00)	1368/7308 (18.72)	406/2111 (19.23)	Χ2 1=0.28, P=0.59512
Med benzodiazepine use : Yes	9419 (100.00)	698/7308 (9.55)	196/2111 (9.28)	Χ2 1=0.14, P=0.71292
Maternal morbidity : Yes	9419 (100.00)	490/7308 (6.70)	148/2111 (7.01)	Χ2 1=0.24, P=0.62222
Dental pain : Yes	9419 (100.00)	258/7308 (3.53)	94/2111 (4.45)	Χ2 1=3.87, P=0.04902
Alcohol use disorder : Yes	9419 (100.00)	419/7308 (5.73)	145/2111 (6.87)	Χ2 1=3.75, P=0.05282
Med anticonvulsant use : Yes	9419 (100.00)	404/7308 (5.53)	93/2111 (4.41)	Χ2 1=4.13, P=0.04212
Med muscle relaxant use : Yes	9419 (100.00)	316/7308 (4.32)	139/2111 (6.58)	Χ2 1=18.21, P<0.00012
Personality disorder : Yes	9419 (100.00)	174/7308 (2.38)	74/2111 (3.51)	Χ2 1=8.08, P=0.00452
Fibromyalgia : Yes	9419 (100.00)	350/7308 (4.79)	108/2111 (5.12)	Χ2 1=0.38, P=0.53862
CDC SVI overall percentile ranking of all 4 themes	8781 (93.23)			F1,8779=3.23, P=0.07253
Median (interquartile range)		0.57 (0.37—0.78)	0.60 (0.38—0.79)
Range		0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.4.2 Three categories

	N	Only pre	Only post	Both pre and post	Test Statistic
		(N=1236)	(N=875)	(N=7308)
Year of delivery	9419 (100.00)				F2,9416=9.21, P=0.00011
Median (interquartile range)		2016 (2015—2018)	2016 (2013—2019)	2016 (2014—2018)
Range		2007—2020	2007—2020	2007—2020
Year of delivery as categorical	9419 (100.00)				Χ2 26=218.72, P<0.00012
2007		3/1236 (0.24)	14/875 (1.60)	37/7308 (0.51)
2008		10/1236 (0.81)	35/875 (4.00)	80/7308 (1.09)
2009		16/1236 (1.29)	30/875 (3.43)	135/7308 (1.85)
2010		19/1236 (1.54)	49/875 (5.60)	217/7308 (2.97)
2011		40/1236 (3.24)	35/875 (4.00)	265/7308 (3.63)
2012		46/1236 (3.72)	31/875 (3.54)	364/7308 (4.98)
2013		69/1236 (5.58)	63/875 (7.20)	577/7308 (7.90)
2014		105/1236 (8.50)	72/875 (8.23)	787/7308 (10.77)
2015		161/1236 (13.03)	81/875 (9.26)	962/7308 (13.16)
2016		186/1236 (15.05)	75/875 (8.57)	874/7308 (11.96)
2017		166/1236 (13.43)	91/875 (10.40)	729/7308 (9.98)
2018		175/1236 (14.16)	68/875 (7.77)	721/7308 (9.87)
2019		133/1236 (10.76)	108/875 (12.34)	737/7308 (10.08)
2020		107/1236 (8.66)	123/875 (14.06)	823/7308 (11.26)
Age at delivery	9419 (100.00)				F2,9416=3.09, P=0.04551
Median (interquartile range)		27 (24—30)	27 (24—31)	27 (24—31)
Range		17—43	17—44	17—44
Number of Gestation weeks	9419 (100.00)				F2,9416=8.87, P=0.00011
Median (interquartile range)		39 (37—39)	38 (37—39)	39 (37—39)
Range		24—42	23—42	21—42
Race	9385 (99.64)				Χ2 8=10.64, P=0.22272
American Indian or Alaska Native		4/1233 (0.32)	3/870 (0.34)	17/7282 (0.23)
Asian or Pacific Islander		1/1233 (0.08)	1/870 (0.11)	10/7282 (0.14)
Black of African American		45/1233 (3.65)	27/870 (3.10)	180/7282 (2.47)
Other or Unknown		13/1233 (1.05)	5/870 (0.57)	44/7282 (0.60)
White		1170/1233 (94.89)	834/870 (95.86)	7031/7282 (96.55)
Hispanic : Not Hispanic	9378 (99.56)	1220/1230 (99.19)	863/869 (99.31)	7215/7279 (99.12)	Χ2 2=0.35, P=0.83782
Race/Ethnicity combined	9385 (99.64)				Χ2 8=13.38, P=0.09962
Hispanic		10/1233 (0.81)	6/870 (0.69)	64/7282 (0.88)
Non-Hispanic Asian		1/1233 (0.08)	1/870 (0.11)	9/7282 (0.12)
Non-Hispanic Black		44/1233 (3.57)	26/870 (2.99)	180/7282 (2.47)
Non-Hispanic Other		15/1233 (1.22)	7/870 (0.80)	40/7282 (0.55)
Non-Hispanic White		1163/1233 (94.32)	830/870 (95.40)	6989/7282 (95.98)
Route of delivery : Vaginal	9385 (99.64)	843/1233 (68.37)	576/870 (66.21)	4703/7282 (64.58)	Χ2 2=7.07, P=0.02922
Number of previous pregnancies	9219 (97.88)				F2,9216=0.01, P=0.98961
Median (interquartile range)		2 (1—3)	2 (1—3)	2 (1—3)
Range		0—19	0—23	0—23
Final outcome	9419 (100.00)				Χ2 6=32.89, P<0.00012
Death		3/1236 (0.24)	6/875 (0.69)	30/7308 (0.41)
Overdose		20/1236 (1.62)	17/875 (1.94)	72/7308 (0.99)
Loss of enrollment		155/1236 (12.54)	134/875 (15.31)	770/7308 (10.54)
Censored		1058/1236 (85.60)	718/875 (82.06)	6436/7308 (88.07)
Final outcome 3 levels	9419 (100.00)				Χ2 4=11.37, P=0.02272
Death		3/1236 (0.24)	6/875 (0.69)	30/7308 (0.41)
Overdose		20/1236 (1.62)	17/875 (1.94)	72/7308 (0.99)
Censored		1213/1236 (98.14)	852/875 (97.37)	7206/7308 (98.60)
Total days supplied MOUD	9419 (100.00)				F2,9416=3650.52, P<0.00011
Median (interquartile range)		30 (14—56)	28 (14—32)	108 (85—122)
Range		1—90	1—70	2—132
Total days supplied MOUD before delivery	9419 (100.00)				F2,9416=3155.82, P<0.00011
Median (interquartile range)		30 (14—56)	0 (0—0)	84 (60—90)
Range		1—90	0—28	1—90
Total days supplied MOUD after delivery	9419 (100.00)				F2,9416=2017.05, P<0.00011
Median (interquartile range)		0 (0—0)	28 (14—32)	30 (21—42)
Range		0—0	1—42	0—42
Total days supplied MOUD (method 2)	9419 (100.00)				F2,9416=3581.34, P<0.00011
Median (interquartile range)		30 (14—56)	28 (14—32)	112 (85—129)
Range		1—132	1—70	2—132
Total days supplied MOUD before delivery (method 2)	9419 (100.00)				F2,9416=3155.82, P<0.00011
Median (interquartile range)		30 (14—56)	0 (0—0)	84 (60—90)
Range		1—90	0—28	1—90
Total days supplied MOUD after delivery (method 2)	9419 (100.00)				F2,9416=2207.37, P<0.00011
Median (interquartile range)		0 (0—0)	28 (14—32)	35 (24—42)
Range		0—42	1—42	0—42
Total days supplied MOUD (method 3)	9419 (100.00)				F2,9416=3733.50, P<0.00011
Median (interquartile range)		30 (14—47)	14 (7—24)	100 (76—116)
Range		1—89	1—41	2—132
Total days supplied MOUD before delivery (method 3)	9419 (100.00)				F2,9416=2728.73, P<0.00011
Median (interquartile range)		30 (14—47)	0 (0—0)	69 (49—80)
Range		1—89	0—0	1—90
Total days supplied MOUD after delivery (method 3)	9419 (100.00)				F2,9416=3476.87, P<0.00011
Median (interquartile range)		0 (0—0)	14 (7—24)	35 (23—41)
Range		0—0	1—41	1—42
Avg dose pre-delivery (mg)	9327 (99.02)				F2,9324=1471.35, P<0.00011
Median (interquartile range)		14.00 (8.00—16.00)	0.00 (0.00—0.00)	14.90 (9.76—16.00)
Range		0.00—50.00	0.00—0.00	0.25—50.00
Avg dose post-delivery (mg)	9327 (99.02)				F2,9324=2011.71, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	16.00 (8.40—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—53.57	0.00—50.00
Avg dose exposure (mg)	9327 (99.02)				F2,9324=21.40, P<0.00011
Median (interquartile range)		14.00 (8.00—16.00)	16.00 (8.40—16.00)	14.02 (9.83—16.00)
Range		0.00—50.00	0.00—53.57	0.25—50.00
Total days buprenorphine before delivery (method 3)	9187 (97.54)				F2,9184=2397.26, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	0.00 (0.00—0.00)	69.00 (49.00—80.00)
Range		1.00—89.00	0.00—0.00	0.00—90.00
Total days buprenorphine after delivery (method 3)	9187 (97.54)				F2,9184=3179.55, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	14.00 (7.00—24.00)	35.00 (23.00—41.00)
Range		0.00—0.00	1.00—41.00	0.00—42.00
Total days supplied buprenorphine	9187 (97.54)				F2,9184=3325.60, P<0.00011
Median (interquartile range)		30.00 (14.00—47.00)	14.00 (7.00—24.00)	100.00 (76.00—116.00)
Range		1.00—89.00	1.00—41.00	2.00—132.00
Avg dose BUP pre-delivery (mg)	9186 (97.53)				F2,9183=1415.08, P<0.00011
Median (interquartile range)		13.38 (8.00—16.00)	0.00 (0.00—0.00)	14.77 (9.54—16.00)
Range		0.00—32.00	0.00—0.00	0.00—40.00
Avg dose BUP post-delivery (mg)	9186 (97.53)				F2,9183=1936.83, P<0.00011
Median (interquartile range)		0.00 (0.00—0.00)	16.00 (8.40—16.00)	12.00 (8.00—16.00)
Range		0.00—0.00	0.00—42.67	0.00—33.24
Avg dose BUP exposure (mg)	9186 (97.53)				F2,9183=17.50, P<0.00011
Median (interquartile range)		13.38 (8.00—16.00)	16.00 (8.40—16.00)	13.95 (9.71—16.00)
Range		0.00—32.00	0.00—42.67	0.25—34.47
Combined pain : Yes	9419 (100.00)	948/1236 (76.70)	651/875 (74.40)	5617/7308 (76.86)	Χ2 2=2.65, P=0.26622
Schizophrenia or personality disorder : Yes	9419 (100.00)	98/1236 (7.93)	85/875 (9.71)	496/7308 (6.79)	Χ2 2=11.11, P=0.00392
Alcohol or other substance use : Yes	9419 (100.00)	549/1236 (44.42)	383/875 (43.77)	3077/7308 (42.10)	Χ2 2=2.89, P=0.23582
Benzodiazepine or anticonvulsant use : Yes	9419 (100.00)	160/1236 (12.94)	112/875 (12.80)	1034/7308 (14.15)	Χ2 2=2.20, P=0.33292
Maternal morbidity : Yes	9419 (100.00)	87/1236 (7.04)	61/875 (6.97)	490/7308 (6.70)	Χ2 2=0.25, P=0.88412
Anxiety and depression combined : Yes	9419 (100.00)	510/1236 (41.26)	414/875 (47.31)	3174/7308 (43.43)	Χ2 2=7.71, P=0.02122
Back pain : Yes	9419 (100.00)	416/1236 (33.66)	273/875 (31.20)	2516/7308 (34.43)	Χ2 2=3.71, P=0.15612
Depression : Yes	9419 (100.00)	431/1236 (34.87)	367/875 (41.94)	2700/7308 (36.95)	Χ2 2=11.49, P=0.00322
Bipolar disorder : Yes	9419 (100.00)	133/1236 (10.76)	72/875 (8.23)	713/7308 (9.76)	Χ2 2=3.74, P=0.15432
Other substance use : Yes	9419 (100.00)	536/1236 (43.37)	366/875 (41.83)	2924/7308 (40.01)	Χ2 2=5.52, P=0.06342
Tobacco use : Yes	9419 (100.00)	864/1236 (69.90)	548/875 (62.63)	4874/7308 (66.69)	Χ2 2=12.24, P=0.00222
Med NSAIDS : Yes	9419 (100.00)	749/1236 (60.60)	524/875 (59.89)	4469/7308 (61.15)	Χ2 2=0.61, P=0.73882
Schizophrenia psychotic disorders : Yes	9419 (100.00)	78/1236 (6.31)	65/875 (7.43)	401/7308 (5.49)	Χ2 2=6.16, P=0.04592
Anxiety : Yes	9419 (100.00)	246/1236 (19.90)	160/875 (18.29)	1368/7308 (18.72)	Χ2 2=1.16, P=0.56022
Med benzodiazepine use : Yes	9419 (100.00)	118/1236 (9.55)	78/875 (8.91)	698/7308 (9.55)	Χ2 2=0.37, P=0.82942
Maternal morbidity : Yes	9419 (100.00)	87/1236 (7.04)	61/875 (6.97)	490/7308 (6.70)	Χ2 2=0.25, P=0.88412
Dental pain : Yes	9419 (100.00)	55/1236 (4.45)	39/875 (4.46)	258/7308 (3.53)	Χ2 2=3.87, P=0.14412
Alcohol use disorder : Yes	9419 (100.00)	74/1236 (5.99)	71/875 (8.11)	419/7308 (5.73)	Χ2 2=7.87, P=0.01962
Med anticonvulsant use : Yes	9419 (100.00)	54/1236 (4.37)	39/875 (4.46)	404/7308 (5.53)	Χ2 2=4.14, P=0.12632
Med muscle relaxant use : Yes	9419 (100.00)	72/1236 (5.83)	67/875 (7.66)	316/7308 (4.32)	Χ2 2=21.95, P<0.00012
Personality disorder : Yes	9419 (100.00)	38/1236 (3.07)	36/875 (4.11)	174/7308 (2.38)	Χ2 2=10.24, P=0.00602
Fibromyalgia : Yes	9419 (100.00)	63/1236 (5.10)	45/875 (5.14)	350/7308 (4.79)	Χ2 2=0.38, P=0.82682
CDC SVI overall percentile ranking of all 4 themes	8781 (93.23)				F2,8778=5.13, P=0.00591
Median (interquartile range)		0.62 (0.40—0.81)	0.57 (0.36—0.76)	0.57 (0.37—0.78)
Range		0.00—1.00	0.00—1.00	0.00—1.00

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

3.5 Histogram of MOUD days supplied

3.5.1 Before delivery up to 90 days (Method 1)

3.5.2 Before delivery up to 90 days (Method 2)

3.5.3 Before delivery up to 90 days (Method 3)

3.5.4 After delivery up to 41 days (Method 1)

3.5.5 After delivery up to 41 days (Method 3)

3.5.6 After delivery up to 41 days (Method 3)

3.5.7 Entire exposure (Method 1)

3.5.8 Entire exposure (Method 2)

3.5.9 Entire exposure (Method 3)

Survival Analysis

3.6 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud)

        n events median 0.95LCL 0.95UCL
[1,] 9419    148     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0    92.5   184.5   176.2   258.8   323.0 

time	probability
2	0.9998938
7	0.9997877
8	0.9995753
10	0.9994692
17	0.9993630
18	0.9992568
19	0.9991507
27	0.9990445
32	0.9989383
34	0.9988321
35	0.9986198
38	0.9985136
41	0.9984075
42	0.9983013
43	0.9981951
45	0.9979828
47	0.9978766
52	0.9976643
59	0.9974520
60	0.9973458
61	0.9972396
63	0.9971335
65	0.9970273
66	0.9969211
69	0.9968149
70	0.9967088
72	0.9966026
75	0.9964964
77	0.9963903
87	0.9962841
91	0.9961779
93	0.9960718
95	0.9959656
97	0.9958594
101	0.9956471
110	0.9955409
111	0.9954348
112	0.9953286
118	0.9951163
120	0.9950101
121	0.9949039
125	0.9947977
128	0.9946916
131	0.9945854
138	0.9943731
140	0.9942669
144	0.9941607
147	0.9940546
151	0.9938422
153	0.9937361
156	0.9935237
166	0.9934176
169	0.9933114
171	0.9932052
173	0.9930991
175	0.9929929
177	0.9928867
178	0.9927805
180	0.9926744
181	0.9925682
182	0.9924620
184	0.9923559
185	0.9922497
188	0.9920374
193	0.9919312
199	0.9918250
204	0.9917189
208	0.9916127
211	0.9915065
213	0.9912942
214	0.9911880
215	0.9909757
216	0.9908695
217	0.9906572
220	0.9905510
222	0.9904448
223	0.9903387
228	0.9901263
229	0.9900202
233	0.9899140
235	0.9898078
236	0.9897017
239	0.9895955
240	0.9893832
242	0.9892770
244	0.9891708
245	0.9890647
246	0.9888523
247	0.9887462
250	0.9886400
253	0.9885338
254	0.9884276
258	0.9883215
261	0.9881091
262	0.9880030
263	0.9878968
265	0.9877906
267	0.9876845
268	0.9875783
270	0.9873660
271	0.9872598
272	0.9871536
274	0.9869413
275	0.9868351
279	0.9867290
281	0.9866228
287	0.9864104
289	0.9863043
290	0.9861981
295	0.9859858
296	0.9858796
298	0.9856673
300	0.9855611
301	0.9854549
302	0.9853488
304	0.9852426
305	0.9851364
308	0.9849241
310	0.9847118
313	0.9846056
316	0.9844994
319	0.9843932
321	0.9842871
323	0.9842871

3.7 Time to event for overdose and death

deathod$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
148	0	123	1	177.3	177.5	108.5	21.8	41.7	94.5	188.0	261.0	296.6	307.0

lowest : 2 7 8 10 17 , highest: 310 313 316 319 321 death$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
39	0	38	1	156.7	156.5	112.7	18.8	34.4	60.0	171.0	243.5	279.4	290.5

lowest : 2 17 19 32 35 , highest: 279 281 290 295 308 od$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
109	0	98	1	184.7	185.5	106.5	29.8	44.6	111.0	208.0	262.0	300.2	309.2

lowest : 7 8 10 18 27 , highest: 310 313 316 319 321

4 Multivariable Cox PH model

4.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.34710	0.07975	0.190800	0.50340
Hazard Ratio	2016	2018	2	1.41500		1.210000	1.65400
Total days supplied MOUD (method 3)	1	31	30	-0.16070	0.06057	-0.279400	-0.04199
Hazard Ratio	1	31	30	0.85150		0.756200	0.95890
Age at delivery	27	31	4	-0.06024	0.07177	-0.200900	0.08043
Hazard Ratio	27	31	4	0.94150		0.818000	1.08400
Number of Gestation weeks	39	37	-2	0.12700	0.06268	0.004138	0.24980
Hazard Ratio	39	37	-2	1.13500		1.004000	1.28400
Route of delivery --- Cesarean:Vaginal	2	1		-0.01680	0.17710	-0.364000	0.33040
Hazard Ratio	2	1		0.98330		0.694900	1.39100
Combined pain --- Yes:No	1	2		-0.16520	0.18680	-0.531300	0.20100
Hazard Ratio	1	2		0.84770		0.587800	1.22300
Alcohol or other substance use --- Yes:No	1	2		0.23270	0.17130	-0.103000	0.56840
Hazard Ratio	1	2		1.26200		0.902100	1.76600
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31120	0.21330	-0.106900	0.72920
Hazard Ratio	1	2		1.36500		0.898600	2.07300
Anxiety and depression combined --- Yes:No	1	2		0.60410	0.18190	0.247600	0.96060
Hazard Ratio	1	2		1.83000		1.281000	2.61300
Maternal morbidity --- Yes:No	1	2		-0.04804	0.35280	-0.739500	0.64340
Hazard Ratio	1	2		0.95310		0.477400	1.90300

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	18.91	1	<0.0001
Total days supplied MOUD (method 3)	7.04	1	0.0080
Age at delivery	0.71	1	0.4008
Route of delivery	0.01	1	0.9245
Number of Gestation weeks	4.11	1	0.0426
Combined pain	0.78	1	0.3767
Alcohol or other substance use	1.85	1	0.1741
Benzodiazepine or anticonvulsant use	2.13	1	0.1443
Anxiety and depression combined	11.02	1	0.0009
Maternal morbidity	0.02	1	0.8916
TOTAL	66.47	10	<0.0001

4.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.1902	0.06096	-0.3097	-0.07073
Hazard Ratio	1	31	30	0.8268		0.7337	0.93170

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	9.73	1	0.0018
TOTAL	9.73	1	0.0018

4.2 With splines

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.41750	0.09150	0.238200	0.59680
Hazard Ratio	2016	2018	2	1.51800		1.269000	1.81600
Total days supplied MOUD (method 3)	1	31	30	-0.16190	0.06003	-0.279600	-0.04427
Hazard Ratio	1	31	30	0.85050		0.756100	0.95670
Age at delivery	27	31	4	-0.06320	0.07159	-0.203500	0.07711
Hazard Ratio	27	31	4	0.93880		0.815900	1.08000
Number of Gestation weeks	39	37	-2	0.12540	0.06314	0.001628	0.24910
Hazard Ratio	39	37	-2	1.13400		1.002000	1.28300
Route of delivery --- Cesarean:Vaginal	2	1		-0.01591	0.17710	-0.362900	0.33110
Hazard Ratio	2	1		0.98420		0.695600	1.39300
Combined pain --- Yes:No	1	2		-0.17350	0.18760	-0.541100	0.19410
Hazard Ratio	1	2		0.84070		0.582100	1.21400
Alcohol or other substance use --- Yes:No	1	2		0.24170	0.17250	-0.096380	0.57990
Hazard Ratio	1	2		1.27300		0.908100	1.78600
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.32850	0.21650	-0.095710	0.75280
Hazard Ratio	1	2		1.38900		0.908700	2.12300
Anxiety and depression combined --- Yes:No	1	2		0.60190	0.18200	0.245200	0.95860
Hazard Ratio	1	2		1.82600		1.278000	2.60800
Maternal morbidity --- Yes:No	1	2		-0.05088	0.35190	-0.740600	0.63890
Hazard Ratio	1	2		0.95040		0.476800	1.89400

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	26.17	2	<0.0001
Nonlinear	1.35	1	0.2452
Total days supplied MOUD (method 3)	7.27	1	0.0070
Age at delivery	0.78	1	0.3769
Route of delivery	0.01	1	0.9284
Number of Gestation weeks	3.95	1	0.0469
Combined pain	0.86	1	0.3550
Alcohol or other substance use	1.96	1	0.1610
Benzodiazepine or anticonvulsant use	2.31	1	0.1287
Anxiety and depression combined	10.92	1	0.0009
Maternal morbidity	0.02	1	0.8850
TOTAL	76.10	11	<0.0001

4.3 Linear model (only buprenorphine)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.36210	0.08162	0.20220	0.52210
Hazard Ratio	2016	2018	2	1.43600		1.22400	1.68600
Total days supplied buprenorphine	1	31	30	-0.19660	0.06203	-0.31820	-0.07508
Hazard Ratio	1	31	30	0.82150		0.72740	0.92770
Age at delivery	27	31	4	-0.05486	0.07259	-0.19710	0.08741
Hazard Ratio	27	31	4	0.94660		0.82110	1.09100
Number of Gestation weeks	39	37	-2	0.13410	0.06190	0.01277	0.25540
Hazard Ratio	39	37	-2	1.14400		1.01300	1.29100
Route of delivery --- Cesarean:Vaginal	2	1		-0.08087	0.18020	-0.43410	0.27240
Hazard Ratio	2	1		0.92230		0.64780	1.31300
Combined pain --- Yes:No	1	2		-0.16840	0.18780	-0.53650	0.19960
Hazard Ratio	1	2		0.84500		0.58480	1.22100
Alcohol or other substance use --- Yes:No	1	2		0.30260	0.17270	-0.03579	0.64100
Hazard Ratio	1	2		1.35300		0.96480	1.89800
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.32320	0.21400	-0.09621	0.74250
Hazard Ratio	1	2		1.38100		0.90830	2.10100
Anxiety and depression combined --- Yes:No	1	2		0.60400	0.18240	0.24640	0.96150
Hazard Ratio	1	2		1.82900		1.27900	2.61600
Maternal morbidity --- Yes:No	1	2		-0.04485	0.35360	-0.73790	0.64820
Hazard Ratio	1	2		0.95610		0.47810	1.91200

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.65	1	<0.0001
Total days supplied buprenorphine	10.05	1	0.0015
Age at delivery	0.57	1	0.4494
Route of delivery	0.20	1	0.6538
Number of Gestation weeks	4.70	1	0.0301
Combined pain	0.80	1	0.3698
Alcohol or other substance use	3.07	1	0.0795
Benzodiazepine or anticonvulsant use	2.28	1	0.1306
Anxiety and depression combined	10.94	1	0.0009
Maternal morbidity	0.02	1	0.8990
TOTAL	70.46	10	<0.0001

4.3.1 Univariate

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.2250	0.06256	-0.3477	-0.1024
Hazard Ratio	1	31	30	0.7985		0.7063	0.9026

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied buprenorphine	12.93	1	0.0003
TOTAL	12.93	1	0.0003

By MOUD timing

5 Survival analysis

5.1 KM Curves

time	probability
2	0.9991909
8	0.9983819
19	0.9975728
32	0.9967638
45	0.9959547
70	0.9951456
97	0.9943366
101	0.9935275
111	0.9927184
125	0.9919094
131	0.9911003
173	0.9902913
177	0.9894822
217	0.9886731
222	0.9878641
240	0.9870550
244	0.9862460
258	0.9854369
261	0.9846278
270	0.9838188
274	0.9830097
287	0.9822006
310	0.9813916
323	0.9813916
27	0.9988571
35	0.9977143
77	0.9965714
87	0.9954286
91	0.9942857
101	0.9931429
118	0.9920000
138	0.9908571
147	0.9897143
166	0.9885714
193	0.9874286
213	0.9862857
215	0.9851429
217	0.9840000
245	0.9828571
270	0.9817143
272	0.9805714
281	0.9794286
295	0.9771429
300	0.9760000
301	0.9748571
319	0.9737143
323	0.9737143
7	0.9998632
8	0.9997263
10	0.9995895
17	0.9994527
18	0.9993158
34	0.9991790
35	0.9990421
38	0.9989053
41	0.9987685
42	0.9986316
43	0.9984948
45	0.9983580
47	0.9982211
52	0.9979475
59	0.9976738
60	0.9975369
61	0.9974001
63	0.9972633
65	0.9971264
66	0.9969896
69	0.9968528
72	0.9967159
75	0.9965791
93	0.9964423
95	0.9963054
110	0.9961686
112	0.9960317
118	0.9958949
120	0.9957581
121	0.9956212
128	0.9954844
138	0.9953476
140	0.9952107
144	0.9950739
151	0.9948002
153	0.9946634
156	0.9943897
169	0.9942529
171	0.9941160
175	0.9939792
178	0.9938424
180	0.9937055
181	0.9935687
182	0.9934319
184	0.9932950
185	0.9931582
188	0.9928845
199	0.9927477
204	0.9926108
208	0.9924740
211	0.9923372
213	0.9922003
214	0.9920635
215	0.9919267
216	0.9917898
220	0.9916530
223	0.9915161
228	0.9912425
229	0.9911056
233	0.9909688
235	0.9908320
236	0.9906951
239	0.9905583
240	0.9904215
242	0.9902846
246	0.9900109
247	0.9898741
250	0.9897373
253	0.9896004
254	0.9894636
261	0.9893268
262	0.9891899
263	0.9890531
265	0.9889163
267	0.9887794
268	0.9886426
271	0.9885057
274	0.9883689
275	0.9882321
279	0.9880952
287	0.9879584
289	0.9878216
290	0.9876847
296	0.9875479
298	0.9872742
302	0.9871374
304	0.9870005
305	0.9868637
308	0.9865900
310	0.9864532
313	0.9863164
316	0.9861795
321	0.9860427
323	0.9860427

5.2 Log-Rank Test

Call:
survdiff(formula = Surv(days.to.event, outcome.bin) ~ moud.both3div, 
    data = moud)

                                   N Observed Expected (O-E)^2/E (O-E)^2/V
moud.both3div=Only pre          1236       23     19.4     0.678     0.781
moud.both3div=Only post          875       23     13.7     6.327     6.973
moud.both3div=Both pre and post 7308      102    114.9     1.455     6.514

 Chisq= 8.5  on 2 degrees of freedom, p= 0.01 

5.3 Multivariable Cox PH model

Linear continuous terms (timing + days)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.124000	0.09142	-0.30320000	0.05513
Hazard Ratio	1	31	30	0.883300		0.73840000	1.05700
Year of delivery	2016	2018	2	0.347500	0.07864	0.19340000	0.50170
Hazard Ratio	2016	2018	2	1.416000		1.21300000	1.65100
Age at delivery	27	31	4	-0.062580	0.07165	-0.20300000	0.07786
Hazard Ratio	27	31	4	0.939300		0.81630000	1.08100
Number of Gestation weeks	39	37	-2	0.121700	0.06215	-0.00008249	0.24360
Hazard Ratio	39	37	-2	1.129000		0.99990000	1.27600
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.006582	0.30350	-0.58820000	0.60140
Hazard Ratio	3	1		1.007000		0.55530000	1.82500
MOUD receipt timing --- Only post:Both pre and post	3	2		0.266400	0.31910	-0.35900000	0.89190
Hazard Ratio	3	2		1.305000		0.69830000	2.44000
Route of delivery --- Cesarean:Vaginal	2	1		-0.018150	0.17720	-0.36550000	0.32920
Hazard Ratio	2	1		0.982000		0.69380000	1.39000
Combined pain --- No:Yes	2	1		0.159900	0.18690	-0.20630000	0.52610
Hazard Ratio	2	1		1.173000		0.81360000	1.69200
Alcohol or other substance use --- Yes:No	1	2		0.239000	0.17120	-0.09651000	0.57450
Hazard Ratio	1	2		1.270000		0.90800000	1.77600
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.313800	0.21310	-0.10400000	0.73150
Hazard Ratio	1	2		1.369000		0.90120000	2.07800
Anxiety and depression combined --- Yes:No	1	2		0.598900	0.18090	0.24430000	0.95350
Hazard Ratio	1	2		1.820000		1.27700000	2.59500
Maternal morbidity --- Yes:No	1	2		-0.048330	0.35250	-0.73930000	0.64260
Hazard Ratio	1	2		0.952800		0.47740000	1.90100

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	0.98	2	0.6116
Total days supplied MOUD (method 3)	1.84	1	0.1747
Year of delivery	19.50	1	<0.0001
Age at delivery	0.76	1	0.3820
Route of delivery	0.01	1	0.9185
Number of Gestation weeks	3.84	1	0.0500
Combined pain	0.73	1	0.3921
Alcohol or other substance use	1.95	1	0.1625
Benzodiazepine or anticonvulsant use	2.17	1	0.1407
Anxiety and depression combined	10.94	1	0.0009
Maternal morbidity	0.02	1	0.8909
TOTAL	69.95	12	<0.0001

Timing only

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.34930	0.07807	0.196300	0.50230
Hazard Ratio	2016	2018	2	1.41800		1.217000	1.65200
Age at delivery	27	31	4	-0.06905	0.07209	-0.210300	0.07224
Hazard Ratio	27	31	4	0.93330		0.810300	1.07500
Number of Gestation weeks	39	37	-2	0.12560	0.06174	0.004555	0.24660
Hazard Ratio	39	37	-2	1.13400		1.005000	1.28000
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.25220	0.23070	-0.199900	0.70430
Hazard Ratio	3	1		1.28700		0.818800	2.02200
MOUD receipt timing --- Only post:Both pre and post	3	2		0.57090	0.23160	0.116900	1.02500
Hazard Ratio	3	2		1.77000		1.124000	2.78700
Route of delivery --- Cesarean:Vaginal	2	1		-0.02640	0.17670	-0.372700	0.31990
Hazard Ratio	2	1		0.97390		0.688800	1.37700
Combined pain --- No:Yes	2	1		0.16070	0.18690	-0.205600	0.52710
Hazard Ratio	2	1		1.17400		0.814200	1.69400
Alcohol or other substance use --- Yes:No	1	2		0.25800	0.17130	-0.077670	0.59360
Hazard Ratio	1	2		1.29400		0.925300	1.81100
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31440	0.21310	-0.103300	0.73210
Hazard Ratio	1	2		1.36900		0.901900	2.07900
Anxiety and depression combined --- Yes:No	1	2		0.59700	0.18060	0.243000	0.95090
Hazard Ratio	1	2		1.81700		1.275000	2.58800
Maternal morbidity --- Yes:No	1	2		-0.05287	0.35230	-0.743500	0.63770
Hazard Ratio	1	2		0.94850		0.475500	1.89200

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	6.48	2	0.0391
Year of delivery	19.99	1	<0.0001
Age at delivery	0.92	1	0.3377
Route of delivery	0.02	1	0.8813
Number of Gestation weeks	4.14	1	0.0418
Combined pain	0.74	1	0.3898
Alcohol or other substance use	2.27	1	0.1318
Benzodiazepine or anticonvulsant use	2.18	1	0.1398
Anxiety and depression combined	10.92	1	0.0010
Maternal morbidity	0.02	1	0.8806
TOTAL	69.36	11	<0.0001

Linear continuous terms (timing + days BUP)

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied buprenorphine	1	31	30	-0.151000	0.09363	-0.33450	0.032490
Hazard Ratio	1	31	30	0.859800		0.71570	1.033000
Year of delivery	2014	2018	4	0.725300	0.15990	0.41190	1.039000
Hazard Ratio	2014	2018	4	2.065000		1.51000	2.825000
Age at delivery	25	35	10	-0.144400	0.18120	-0.49970	0.210800
Hazard Ratio	25	35	10	0.865500		0.60670	1.235000
Number of Gestation weeks	37	39	2	-0.126900	0.06091	-0.24630	-0.007551
Hazard Ratio	37	39	2	0.880800		0.78170	0.992500
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.003667	0.30750	-0.59890	0.606300
Hazard Ratio	3	1		1.004000		0.54940	1.834000
MOUD receipt timing --- Only post:Both pre and post	3	2		0.360500	0.32610	-0.27870	0.999600
Hazard Ratio	3	2		1.434000		0.75680	2.717000
Route of delivery --- Cesarean:Vaginal	2	1		-0.082460	0.18020	-0.43570	0.270800
Hazard Ratio	2	1		0.920900		0.64680	1.311000
Combined pain --- No:Yes	2	1		0.158900	0.18800	-0.20950	0.527300
Hazard Ratio	2	1		1.172000		0.81100	1.694000
Alcohol or other substance use --- Yes:No	1	2		0.316800	0.17250	-0.02136	0.655000
Hazard Ratio	1	2		1.373000		0.97890	1.925000
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.326200	0.21380	-0.09290	0.745200
Hazard Ratio	1	2		1.386000		0.91130	2.107000
Anxiety and depression combined --- Yes:No	1	2		0.601100	0.18180	0.24470	0.957500
Hazard Ratio	1	2		1.824000		1.27700	2.605000
Maternal morbidity --- Yes:No	1	2		-0.048310	0.35330	-0.74070	0.644100
Hazard Ratio	1	2		0.952800		0.47680	1.904000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	1.77	2	0.4132
Total days supplied buprenorphine	2.60	1	0.1066
Year of delivery	20.55	1	<0.0001
Age at delivery	0.64	1	0.4252
Route of delivery	0.21	1	0.6475
Number of Gestation weeks	4.35	1	0.0370
Combined pain	0.71	1	0.3979
Alcohol or other substance use	3.38	1	0.0662
Benzodiazepine or anticonvulsant use	2.33	1	0.1268
Anxiety and depression combined	10.91	1	0.0010
Maternal morbidity	0.02	1	0.8911
TOTAL	76.10	12	<0.0001

Timing only BUP

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2014	2018	4	0.73050	0.15850	0.419900	1.04100
Hazard Ratio	2014	2018	4	2.07600		1.522000	2.83300
Age at delivery	25	35	10	-0.16380	0.18250	-0.521400	0.19380
Hazard Ratio	25	35	10	0.84890		0.593700	1.21400
Number of Gestation weeks	37	39	2	-0.13200	0.06041	-0.250400	-0.01357
Hazard Ratio	37	39	2	0.87640		0.778500	0.98650
MOUD receipt timing --- Only pre:Both pre and post	3	1		0.30200	0.23150	-0.151700	0.75560
Hazard Ratio	3	1		1.35300		0.859300	2.12900
MOUD receipt timing --- Only post:Both pre and post	3	2		0.72830	0.23700	0.263700	1.19300
Hazard Ratio	3	2		2.07200		1.302000	3.29600
Route of delivery --- Cesarean:Vaginal	2	1		-0.09451	0.17980	-0.446900	0.25790
Hazard Ratio	2	1		0.90980		0.639600	1.29400
Combined pain --- No:Yes	2	1		0.15970	0.18810	-0.208900	0.52830
Hazard Ratio	2	1		1.17300		0.811500	1.69600
Alcohol or other substance use --- Yes:No	1	2		0.34090	0.17320	0.001428	0.68030
Hazard Ratio	1	2		1.40600		1.001000	1.97500
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.32740	0.21380	-0.091680	0.74650
Hazard Ratio	1	2		1.38700		0.912400	2.11000
Anxiety and depression combined --- Yes:No	1	2		0.59910	0.18150	0.243300	0.95490
Hazard Ratio	1	2		1.82000		1.275000	2.59800
Maternal morbidity --- Yes:No	1	2		-0.05515	0.35300	-0.747100	0.63680
Hazard Ratio	1	2		0.94630		0.473700	1.89000

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD receipt timing	9.98	2	0.0068
Year of delivery	21.22	1	<0.0001
Age at delivery	0.81	1	0.3690
Route of delivery	0.28	1	0.5994
Number of Gestation weeks	4.78	1	0.0287
Combined pain	0.72	1	0.3958
Alcohol or other substance use	3.88	1	0.0489
Benzodiazepine or anticonvulsant use	2.35	1	0.1254
Anxiety and depression combined	10.88	1	0.0010
Maternal morbidity	0.02	1	0.8757
TOTAL	75.51	11	<0.0001

6 Sensitivity analysis 2007-2018

6.1 Descriptive Statistics

• There are 5728 pregnancies in 5049 unique individuals

  	N	Overall
  		(N=7388)
  Year of delivery	7388 (100.00)
  Median (interquartile range)		2015 (2013—2017)
  Range		2007—2018
  Age at delivery	7388 (100.00)
  Median (interquartile range)		27 (24—30)
  Range		17—44
  Number of Gestation weeks	7388 (100.00)
  Median (interquartile range)		39 (37—39)
  Range		21—42
  Race	7364 (99.68)
  American Indian or Alaska Native		19/7364 (0.26)
  Asian or Pacific Islander		9/7364 (0.12)
  Black of African American		166/7364 (2.25)
  Other or Unknown		48/7364 (0.65)
  White		7122/7364 (96.71)
  Hispanic : Not Hispanic	7357 (99.58)	7300/7357 (99.23)
  Race/Ethnicity combined	7364 (99.68)
  Hispanic		57/7364 (0.77)
  Non-Hispanic Asian		8/7364 (0.11)
  Non-Hispanic Black		165/7364 (2.24)
  Non-Hispanic Other		51/7364 (0.69)
  Non-Hispanic White		7083/7364 (96.18)
  Route of delivery : Vaginal	7364 (99.68)	4835/7364 (65.66)
  Number of previous pregnancies	7204 (97.51)
  Median (interquartile range)		2 (1—3)
  Range		0—23
  Final outcome	7388 (100.00)
  Death		28/7388 (0.38)
  Overdose		64/7388 (0.87)
  Loss of enrollment		1012/7388 (13.70)
  Censored		6284/7388 (85.06)
  Final outcome (w/o all payer data)	7388 (100.00)
  Death		12/7388 (0.16)
  Overdose		59/7388 (0.80)
  Loss of enrollment		1033/7388 (13.98)
  Censored		6284/7388 (85.06)
  Total days supplied MOUD	7388 (100.00)
  Median (interquartile range)		92 (53—120)
  Range		1—132
  Total days supplied MOUD before delivery	7388 (100.00)
  Median (interquartile range)		73 (32—90)
  Range		0—90
  Total days supplied MOUD after delivery	7388 (100.00)
  Median (interquartile range)		29 (7—41)
  Range		0—42
  Total days supplied MOUD (method 2)	7388 (100.00)
  Median (interquartile range)		96 (53—121)
  Range		1—132
  Total days supplied MOUD before delivery (method 2)	7388 (100.00)
  Median (interquartile range)		73 (32—90)
  Range		0—90
  Total days supplied MOUD after delivery (method 2)	7388 (100.00)
  Median (interquartile range)		30 (10—42)
  Range		0—42
  Total days supplied MOUD (method 3)	7388 (100.00)
  Median (interquartile range)		88 (44—110)
  Range		1—132
  Total days supplied MOUD before delivery (method 3)	7388 (100.00)
  Median (interquartile range)		61 (29—77)
  Range		0—90
  Total days supplied MOUD after delivery (method 3)	7388 (100.00)
  Median (interquartile range)		29 (12—40)
  Range		0—42
  Avg dose pre-delivery (mg)	7321 (99.09)
  Median (interquartile range)		14.32 (8.00—16.00)
  Range		0.00—50.00
  Avg dose post-delivery (mg)	7321 (99.09)
  Median (interquartile range)		9.60 (3.75—16.00)
  Range		0.00—53.57
  Avg dose exposure (mg)	7321 (99.09)
  Median (interquartile range)		14.25 (9.87—16.00)
  Range		0.00—53.57
  Total days buprenorphine before delivery (method 3)	7255 (98.20)
  Median (interquartile range)		62.00 (30.00—77.00)
  Range		0.00—90.00
  Total days buprenorphine after delivery (method 3)	7255 (98.20)
  Median (interquartile range)		29.00 (12.00—40.00)
  Range		0.00—42.00
  Total days supplied buprenorphine	7255 (98.20)
  Median (interquartile range)		88.00 (46.00—110.00)
  Range		1.00—132.00
  Avg dose BUP pre-delivery (mg)	7255 (98.20)
  Median (interquartile range)		14.25 (8.00—16.00)
  Range		0.00—40.00
  Avg dose BUP post-delivery (mg)	7255 (98.20)
  Median (interquartile range)		9.60 (4.00—16.00)
  Range		0.00—42.67
  Avg dose BUP exposure (mg)	7255 (98.20)
  Median (interquartile range)		14.17 (9.75—16.00)
  Range		0.00—42.67
  Combined pain : Yes	7388 (100.00)	5786/7388 (78.32)
  Schizophrenia or personality disorder : Yes	7388 (100.00)	505/7388 (6.84)
  Alcohol or other substance use : Yes	7388 (100.00)	3314/7388 (44.86)
  Benzodiazepine or anticonvulsant use : Yes	7388 (100.00)	1103/7388 (14.93)
  Maternal morbidity : Yes	7388 (100.00)	573/7388 (7.76)
  Anxiety and depression combined : Yes	7388 (100.00)	3031/7388 (41.03)
  Back pain : Yes	7388 (100.00)	3042/7388 (41.17)
  Depression : Yes	7388 (100.00)	2620/7388 (35.46)
  Bipolar disorder : Yes	7388 (100.00)	695/7388 (9.41)
  Other substance use : Yes	7388 (100.00)	3157/7388 (42.73)
  Tobacco use : Yes	7388 (100.00)	5057/7388 (68.45)
  Med NSAIDS : Yes	7388 (100.00)	4425/7388 (59.89)
  Schizophrenia psychotic disorders : Yes	7388 (100.00)	379/7388 (5.13)
  Anxiety : Yes	7388 (100.00)	1163/7388 (15.74)
  Med benzodiazepine use : Yes	7388 (100.00)	750/7388 (10.15)
  Maternal morbidity : Yes	7388 (100.00)	573/7388 (7.76)
  Dental pain : Yes	7388 (100.00)	274/7388 (3.71)
  Alcohol use disorder : Yes	7388 (100.00)	462/7388 (6.25)
  Med anticonvulsant use : Yes	7388 (100.00)	427/7388 (5.78)
  Med muscle relaxant use : Yes	7388 (100.00)	355/7388 (4.81)
  Personality disorder : Yes	7388 (100.00)	209/7388 (2.83)
  Fibromyalgia : Yes	7388 (100.00)	372/7388 (5.04)
  CDC SVI overall percentile ranking of all 4 themes	6837 (92.54)
  Median (interquartile range)		0.57 (0.37—0.78)
  Range		0.00—1.00

  N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

6.1.1 Time to event for overdose and death

deathod18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
92	0	84	1	182.6	183	107.7	23.4	43.2	111.8	193.5	268.5	295.9	305.8

lowest : 2 7 8 18 19 , highest: 304 308 310 316 319 death18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
28	0	27	1	163.7	163.5	118.1	24.60	37.10	58.75	174.50	267.75	283.70	293.25

lowest : 2 19 35 38 45 , highest: 279 281 290 295 308 od18$days.to.event

n	missing	distinct	Info	Mean	pMedian	Gmd	.05	.10	.25	.50	.75	.90	.95
64	0	61	1	190.9	195	102.7	29.25	51.80	123.75	213.00	268.50	300.10	309.10

lowest : 7 8 18 27 42 , highest: 302 304 310 316 319

Survival Analysis

6.2 Kaplan Meier Plot

Call: survfit(formula = Surv(days.to.event, outcome.bin) ~ 1, data = moud18)

        n events median 0.95LCL 0.95UCL
[1,] 7388     92     NA      NA      NA

   Min. 1st Qu.  Median    Mean 3rd Qu.    Max. 
    2.0   111.0   184.0   181.1   268.0   323.0 

time	probability
2	0.9998646
7	0.9997293
8	0.9995939
18	0.9994586
19	0.9993232
27	0.9991879
35	0.9990525
38	0.9989172
42	0.9987818
43	0.9986465
45	0.9985111
47	0.9983757
52	0.9981050
61	0.9979697
63	0.9978343
66	0.9976990
69	0.9975636
72	0.9974283
91	0.9972929
97	0.9971576
110	0.9970222
111	0.9968868
112	0.9967515
118	0.9966161
120	0.9964808
125	0.9963454
128	0.9962101
131	0.9960747
138	0.9958040
140	0.9956687
144	0.9955333
147	0.9953979
156	0.9952626
166	0.9951272
169	0.9949919
171	0.9948565
175	0.9947212
177	0.9945858
178	0.9944505
180	0.9943151
181	0.9941798
182	0.9940444
184	0.9939090
188	0.9937737
199	0.9936383
208	0.9935030
213	0.9932323
215	0.9930969
217	0.9928262
220	0.9926909
222	0.9925555
223	0.9924201
228	0.9922848
229	0.9921494
235	0.9920141
239	0.9918787
240	0.9916080
244	0.9914727
246	0.9913373
258	0.9912019
261	0.9910666
265	0.9909312
267	0.9907959
268	0.9906605
270	0.9903898
271	0.9902545
272	0.9901191
274	0.9899838
275	0.9898484
279	0.9897130
281	0.9895777
287	0.9894423
289	0.9893070
290	0.9891716
295	0.9889009
296	0.9887656
298	0.9886302
301	0.9884949
302	0.9883595
304	0.9882241
308	0.9880888
310	0.9878181
316	0.9876827
319	0.9875474
323	0.9875474

Multivariable Cox PH model

6.2.1 Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.28350	0.11630	0.05561	0.51130
Hazard Ratio	2016	2018	2	1.32800		1.05700	1.66800
Total days supplied MOUD (method 3)	1	31	30	-0.22680	0.07815	-0.38000	-0.07361
Hazard Ratio	1	31	30	0.79710		0.68390	0.92900
Age at delivery	27	31	4	-0.03408	0.09467	-0.21960	0.15150
Hazard Ratio	27	31	4	0.96650		0.80280	1.16400
Number of Gestation weeks	39	37	-2	0.16070	0.07596	0.01186	0.30960
Hazard Ratio	39	37	-2	1.17400		1.01200	1.36300
Route of delivery --- Cesarean:Vaginal	2	1		0.18100	0.21970	-0.24960	0.61150
Hazard Ratio	2	1		1.19800		0.77910	1.84300
Combined pain --- No:Yes	2	1		0.16660	0.25020	-0.32370	0.65690
Hazard Ratio	2	1		1.18100		0.72350	1.92900
Alcohol or other substance use --- Yes:No	1	2		-0.07965	0.21600	-0.50310	0.34380
Hazard Ratio	1	2		0.92340		0.60470	1.41000
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.27200	0.26650	-0.25030	0.79440
Hazard Ratio	1	2		1.31300		0.77850	2.21300
Anxiety and depression combined --- Yes:No	1	2		0.61880	0.22390	0.17990	1.05800
Hazard Ratio	1	2		1.85700		1.19700	2.87900
Maternal morbidity --- Yes:No	1	2		-0.12930	0.42560	-0.96350	0.70490
Hazard Ratio	1	2		0.87870		0.38150	2.02400

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	5.94	1	0.0148
Total days supplied MOUD (method 3)	8.42	1	0.0037
Age at delivery	0.13	1	0.7186
Route of delivery	0.68	1	0.4101
Number of Gestation weeks	4.49	1	0.0342
Combined pain	0.44	1	0.5053
Alcohol or other substance use	0.14	1	0.7122
Benzodiazepine or anticonvulsant use	1.04	1	0.3069
Anxiety and depression combined	7.63	1	0.0057
Maternal morbidity	0.09	1	0.7613
TOTAL	44.83	10	<0.0001

6.2.2 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Total days supplied MOUD (method 3)	1	31	30	-0.2464	0.07796	-0.3992	-0.09359
Hazard Ratio	1	31	30	0.7816		0.6709	0.91070

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Total days supplied MOUD (method 3)	9.99	1	0.0016
TOTAL	9.99	1	0.0016

7 Sensitivity analysis shift-forward

	N	Overall
		(N=9419)
Total days supplied MOUD (method 3)	9419 (100.00)
Median (interquartile range)		88 (43—111)
Range		1—132
MOUD days exposure shifted approach	9419 (100.00)
Median (interquartile range)		91 (47—115)
Range		1—132

N is the number of non-missing value. ¹Kruskal-Wallis. ²Pearson. ³Wilcoxon.

7.1 Survival Analysis

Multivariable Cox PH model

Linear continuous terms

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
Year of delivery	2016	2018	2	0.34820	0.07964	0.192200	0.50430
Hazard Ratio	2016	2018	2	1.41700		1.212000	1.65600
MOUD days exposure shifted approach	1	31	30	-0.15140	0.05975	-0.268500	-0.03425
Hazard Ratio	1	31	30	0.85950		0.764500	0.96630
Age at delivery	27	31	4	-0.06034	0.07183	-0.201100	0.08044
Hazard Ratio	27	31	4	0.94140		0.817800	1.08400
Number of Gestation weeks	39	37	-2	0.12750	0.06250	0.005034	0.25000
Hazard Ratio	39	37	-2	1.13600		1.005000	1.28400
Route of delivery --- Cesarean:Vaginal	2	1		-0.01780	0.17710	-0.364900	0.32930
Hazard Ratio	2	1		0.98240		0.694200	1.39000
Combined pain --- No:Yes	2	1		0.16420	0.18680	-0.201900	0.53030
Hazard Ratio	2	1		1.17800		0.817200	1.69900
Alcohol or other substance use --- Yes:No	1	2		0.23750	0.17140	-0.098360	0.57340
Hazard Ratio	1	2		1.26800		0.906300	1.77400
Benzodiazepine or anticonvulsant use --- Yes:No	1	2		0.31020	0.21340	-0.107900	0.72840
Hazard Ratio	1	2		1.36400		0.897700	2.07200
Anxiety and depression combined --- Yes:No	1	2		0.60520	0.18190	0.248800	0.96170
Hazard Ratio	1	2		1.83200		1.282000	2.61600
Maternal morbidity --- Yes:No	1	2		-0.04861	0.35270	-0.739800	0.64260
Hazard Ratio	1	2		0.95260		0.477200	1.90100

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
Year of delivery	19.09	1	<0.0001
MOUD days exposure shifted approach	6.41	1	0.0113
Age at delivery	0.71	1	0.4004
Route of delivery	0.01	1	0.9200
Number of Gestation weeks	4.17	1	0.0411
Combined pain	0.77	1	0.3794
Alcohol or other substance use	1.92	1	0.1656
Benzodiazepine or anticonvulsant use	2.12	1	0.1456
Anxiety and depression combined	11.06	1	0.0009
Maternal morbidity	0.02	1	0.8903
TOTAL	66.36	10	<0.0001

7.1.1 Univariable HR

Effects   Response: Surv(days.to.event, outcome.bin)
	Low	High	Δ	Effect	S.E.	Lower 0.95	Upper 0.95
MOUD days exposure shifted approach	1	31	30	-0.1768	0.06042	-0.2952	-0.05834
Hazard Ratio	1	31	30	0.8380		0.7444	0.94330

Wald Statistics for Surv(days.to.event, outcome.bin)
	χ2	d.f.	P
MOUD days exposure shifted approach	8.55	1	0.0035
TOTAL	8.55	1	0.0035